Visual analysis of pulmonary blood flow in pulmonary circulation assessment: differences between two variant algorithms for processing dynamic images.

Background: In the quantitative assessment of pulmonary blood flow, two different processing algorithms [cross-correlation calculation processing (CCC-pro) and reference frame subtraction processing (RFS-pro)] within dynamic imaging systems have been reported to exhibit high correlations with conventional measurement methods. However, reports still need to evaluate these two processing algorithms regarding the different aspects of pulmonary blood flow. This study aimed to analyze the differences in pulmonary circulation. Methods: We conducted a cross-sectional study to evaluate patients with lung cancer who underwent radical surgery, simultaneous dynamic chest radiography (DCR), and pulmonary perfusion scintigraphy (PPS). We assessed the correlation between PPS and two algorithms (CCC-pro and RFS-pro) regarding calculated blood flow ratio (BFR) using Pearson's correlation and linear regression analysis. Additionally, we evaluated consistency using the Bland-Altman analysis. We compared the pulmonary blood flow distributions across six-division lung fields and evaluated each method's blood flow images and histograms of pixel values. Results: From May 2018 to December 2020, we consecutively enrolled 46 patients with lung cancer who met the inclusion criteria (40 male patients, with a mean age of 72.91 years). In these patients, CCC-pro and RFS-pro were correlated (R=0.718, P<0.01); however, CCC-pro was more strongly correlated with PPS than RFS-pro (R=0.859, P<0.01 vs. R=0.549, P<0.01). The Bland-Altman analysis showed high agreement, although systematic errors were observed in relationships other than RFS-pro to PPS. CCC-pro and RFS-pro showed similar blood flow distributions in the upper and lower lung fields, with RFS-pro being dominant in the middle. RFS-pro showed higher pixel values in the hilar region and a histogram shape similar to PPS; however, posture affected the right upper lung field gradient. RFS-pro showed no difference in the BFR when the pulmonary artery region was symmetric; however, potential inaccuracies existed when it overlapped with the cardiovascular shadow. Conclusions: The CCC-pro algorithm was useful for quantifying BFRs, whereas the RFS-pro algorithm accurately evaluated blood flow distribution in lung fields. Further algorithm development is required to enable versatile pulmonary blood flow analysis.

Total-body dynamic PET/CT imaging reveals kinetic distribution of [13N]NH3 in normal organs.

PURPOSE: To systematically investigate kinetic metrics and metabolic trapping of [13N]NH3 in organs. METHODS: Eleven participants performed total-body [13N]NH3 dynamic positron emission tomography (PET). Regions of interest were drawn in organs to obtain time-to-activity curves (TACs), which were fitted with an irreversible two-tissue compartment model (2TC) to investigate constant rates K1, k2 and k3, and to calculate Ki. Additionally, one-tissue compartment model using full data (1TCfull) and the first four minutes of data (1TC4min) were fitted to TAC data. K1 and k2 were compared among different models to assess [13N]NH3 trapping in organs. RESULTS: Kinetic rates of [13N]NH3 varied significantly among organs. The mean K1 ranged from 0.049 mL/cm3/min in the muscle to 2.936 mL/cm3/min in the kidney. The k2 and k3 were lowest in the liver (0.001 min- 1) and in the pituitary (0.009 min- 1), while highest in the kidney (0.587 min- 1) and in the liver (0.800 min- 1), respectively. The Ki was largest in the myocardium (0.601 ± 0.259 mL/cm3/min) while smallest in the bone marrow (0.028 ± 0.022 mL/cm3/min). Three groups of organs with similar kinetic characteristics were revealed: (1) the thyroid, the lung, the spleen, the pancreas, and the kidney; (2) the liver and the muscle; and (3) the cortex, the white matter, the cerebellum, the pituitary, the parotid, the submandibular gland, the myocardium, the bone, and the bone marrow. Obvious k3 was identified in multiple organs, and significant changes of K1 in multiple organs and k2 in most organs were found between 2TC and 1TCfull, but both K1 and k2 were comparable between 2TC and 1TC4min. CONCLUSION: The kinetic rates of [13N]NH3 differed among organs with some have obvious 13N-anmmonia trapping. The normal distribution of kinetic metrics of 13N-anmmonia in organs can serve as a reference for its potential use in tumor imaging.

Surface-Functionalized Halo-Tag Gold Nanoprobes for Live-Cell Long-Term Super-Resolution Imaging of Endoplasmic Reticulum Dynamics.

Super-resolution fluorescence microscopy has emerged as a powerful tool for studying endoplasmic reticulum (ER) dynamics in living cells. However, the lack of high-brightness, high-photostability, and stable labeling probes makes long-term super-resolution imaging of the ER still challenging. Herein, we reported a surface-functionalized Halo-tag gold nanofluorescent probe (GNP-Atto565-fR8-CA) that exhibits excellent brightness, photostability, and biocompatibility. GNP-Atto565-fR8-CA can simultaneously load multiple Atto565 dye molecules, significantly improving its brightness. Modifying the cell-penetrating peptide fR8 enables GNP-Atto565-fR8-CA to be efficiently delivered into the cytoplasm, overcoming the challenge of their easy entrapment in vesicles. Fluorescent labeling of ER proteins via Halo tags enables high specificity and stable labeling of GNP-Atto565-fR8-CA to the ER. The SIM super-resolution imaging results showed that GNP-Atto565-fR8-CA can track and observe the long-term dynamic process of the ER, and can also be used for long-term super-resolution imaging of the dynamic interactions between the ER and other organelles. This work offers a practical tool to study live-cell ER ultrastructure and dynamics.

The value of net influx constant based on FDG PET/CT dynamic imaging in the differential diagnosis of metastatic from non-metastatic lymph nodes in lung cancer.

OBJECTIVES: This study aims to evaluate the value of the dynamic and static quantitative metabolic parameters derived from 18F-fluorodeoxyglucose (FDG)-positron emission tomography/CT (PET/CT) in the differential diagnosis of metastatic from non-metastatic lymph nodes (LNs) in lung cancer and to validate them based on the results of a previous study. METHODS: One hundred and twenty-one patients with lung nodules or masses detected on chest CT scan underwent 18F-FDG PET/CT dynamic + static imaging with informed consent. A retrospective collection of 126 LNs in 37 patients with lung cancer was pathologically confirmed. Static image analysis parameters include LN-SUVmax and LN-SUVmax/primary tumor SUVmax (LN-SUVmax/PT-SUVmax). Dynamic metabolic parameters including the net influx rate (Ki) and the surrogate of perfusion (K1) and of each LN were obtained by applying the irreversible two-tissue compartment model using in-house Matlab software. Ki/K1 was then calculated as a separate marker. Based on the pathological findings, we divided into a metastatic group and a non-metastatic group. The χ2 test was used to evaluate the agreement of the individual and combined diagnosis of each metabolic parameter with the gold standard. The receiver-operating characteristic (ROC) analysis was performed for each parameter to determine the diagnostic efficacy in differentiating non-metastatic from metastatic LNs with high FDG-avid. P < 0.05 was considered statistically significant. RESULTS: Among the 126 FDG-avid LNs confirmed by pathology, 70 LNs were metastatic, and 56 LNs were non-metastatic. For ROC analysis, in separate assays, the dynamic metabolic parameter Ki [sensitivity (SEN) of 84.30%, specificity (SPE) of 94.60%, accuracy of 88.89%, and AUC of 0.895] had a better diagnostic value than the static metabolic parameter SUVmax (SEN of 82.90%, SPE of 62.50%, accuracy of 74.60%, and AUC of 0.727) in differentiating between metastatic from non-metastatic LNs groups, respectively. In the combined diagnosis group, the combined SUVmax + Ki diagnosis had a better diagnostic value in the differential diagnosis of metastatic from non-metastatic LNs, with SEN, SPE, accuracy, and AUC of 84.3%, 94.6%, 88.89%, and 0.907, respectively. CONCLUSIONS: When the cutoff value of Ki was 0.022 ml/g/min, it had a high diagnostic value in the differential diagnosis between metastasis and non-metastasis in FDG-avid LNs of lung cancer, especially in improving the specificity. The combination of SUVmax and Ki is expected to be a reliable metabolic parameter for N-staging of lung cancer.

Four-dimensional analysis of aortic root motion in normal population using retrospective multiphase computed tomography.

Aims: Aortic root motion is suspected to contribute to proximal aortic dissection. While motion of the aorta in four dimensions can be traced with real-time imaging, displacement and rotation in quantitative terms remain unknown. The hypothesis was to show feasibility of quantification of three-dimensional aortic root motion from dynamic CT imaging. Methods and results: Dynamic CT images of 40 patients for coronary assessment were acquired using a dynamic protocol. Scans were ECG-triggered and segmented in 10 time-stepped phases (0-90%) per cardiac cycle. With identification of the sinotubular junction (STJ), a patient-specific co-ordinate system was created with the z-axis (out-of-plane) parallel to longitudinal direction. The left and right coronary ostia were traced at each time-step to quantify downward motion in reference to the STJ plane, motion within the STJ plane (in-plane), and the degree of rotation. Enrolled individuals had an age of 65 ± 12, and 14 were male (35%). The out-of-plane motion was recorded with the largest displacement of 10.26 ± 2.20 and 8.67 ± 1.69 mm referenced by left and right coronary ostia, respectively. The mean downward movement of aortic root was 9.13 ± 1.86 mm. The largest in-plane motion was recorded at 9.17 ± 2.33 mm and 6.51 ± 1.75 mm referenced by left and right coronary ostia, respectively. The largest STJ in-plane motion was 7.37 ± 1.96 mm, and rotation of the aortic root was 11.8 ± 4.60°. Conclusion: In vivo spatial and temporal displacement of the aortic root can be identified and quantified from multiphase ECG-gated contrast-enhanced CT images. Knowledge of normal 4D motion of the aortic root may help understand its biomechanical impact in patients with aortopathy and pre- and post-surgical or transcatheter aortic valve replacement.

Roentgenoscopy of laser-induced projectile impact testing.

Laser-induced projectile impact testing (LIPIT) based on synchrotron imaging is proposed and validated. This emerging high-velocity, high-strain microscale dynamic loading technique offers a unique perspective on the strain and energy dissipation behavior of materials subjected to high-speed microscale single-particle impacts. When combined with synchrotron radiation imaging techniques, LIPIT allows for in situ observation of particle infiltration. Two validation experiments were carried out, demonstrating the potential of LIPIT in the roentgenoscopy of the dynamic properties of various materials. With a spatial resolution of 10 µm and a temporal resolution of 33.4 µs, the system was successfully realized at the Beijing Synchrotron Radiation Facility 3W1 beamline. This innovative approach opens up new avenues for studying the dynamic properties of materials in situ.

Measurement of Scapholunate Joint Space Width on Real-Time MRI-A Feasibility Study.

INTRODUCTION: The scapholunate interosseous ligament is pivotal for wrist stability, and its impairment can result in instability and joint degeneration. This study explores the application of real-time MRI for dynamic assessment of the scapholunate joint during wrist motion with the objective of determining its diagnostic value in efficacy in contrast to static imaging modalities. MATERIALS AND METHODS: Ten healthy participants underwent real-time MRI scans during wrist ab/adduction and fist-clenching maneuvers. Measurements were obtained at proximal, medial, and distal landmarks on both dynamic and static images with statistical analyses conducted to evaluate the reliability of measurements at each landmark and the concordance between dynamic measurements and established static images. Additionally, inter- and intraobserver variabilities were evaluated. RESULTS: Measurements of the medial landmarks demonstrated the closest agreement with static images and exhibited the least scatter. Distal landmark measurements showed a similar level of agreement but with increased scatter. Proximal landmark measurements displayed substantial deviation, which was accompanied by an even greater degree of scatter. Although no significant differences were observed between the ab/adduction and fist-clenching maneuvers, both inter- and intraobserver variabilities were significant across all measurements. CONCLUSIONS: This study highlights the potential of real-time MRI in the dynamic assessment of the scapholunate joint particularly at the medial landmark. Despite promising results, challenges such as measurement variability need to be addressed. Standardization and integration with advanced image processing methods could significantly enhance the accuracy and reliability of real-time MRI, paving the way for its clinical implementation in dynamic wrist imaging studies.

Intraoperative near infrared functional imaging of rectal cancer using artificial intelligence methods - now and near future state of the art.

Colorectal cancer remains a major cause of cancer death and morbidity worldwide. Surgery is a major treatment modality for primary and, increasingly, secondary curative therapy. However, with more patients being diagnosed with early stage and premalignant disease manifesting as large polyps, greater accuracy in diagnostic and therapeutic precision is needed right from the time of first endoscopic encounter. Rapid advancements in the field of artificial intelligence (AI), coupled with widespread availability of near infrared imaging (currently based around indocyanine green (ICG)) can enable colonoscopic tissue classification and prognostic stratification for significant polyps, in a similar manner to contemporary dynamic radiological perfusion imaging but with the advantage of being able to do so directly within interventional procedural time frames. It can provide an explainable method for immediate digital biopsies that could guide or even replace traditional forceps biopsies and provide guidance re margins (both areas where current practice is only approximately 80% accurate prior to definitive excision). Here, we discuss the concept and practice of AI enhanced ICG perfusion analysis for rectal cancer surgery while highlighting recent and essential near-future advancements. These include breakthrough developments in computer vision and time series analysis that allow for real-time quantification and classification of fluorescent perfusion signals of rectal cancer tissue intraoperatively that accurately distinguish between normal, benign, and malignant tissues in situ endoscopically, which are now undergoing international prospective validation (the Horizon Europe CLASSICA study). Next stage advancements may include detailed digital characterisation of small rectal malignancy based on intraoperative assessment of specific intratumoral fluorescent signal pattern. This could include T staging and intratumoral molecular process profiling (e.g. regarding angiogenesis, differentiation, inflammatory component, and tumour to stroma ratio) with the potential to accurately predict the microscopic local response to nonsurgical treatment enabling personalised therapy via decision support tools. Such advancements are also applicable to the next generation fluorophores and imaging agents currently emerging from clinical trials. In addition, by providing an understandable, applicable method for detailed tissue characterisation visually, such technology paves the way for acceptance of other AI methodology during surgery including, potentially, deep learning methods based on whole screen/video detailing.

Wearing an ultrasound probe during walking does not influence lower limb joint kinematics in adolescents with cerebral palsy and typically developing peers.

BACKGROUND: Enhancing traditional three-dimensional gait analysis with a portable ultrasound device at the lower-limb muscle-tendon level enables direct measurement of muscle and tendon lengths during walking. However, it is important to consider that the size of the ultrasound probe and its attachment on the lower limb may potentially influence gait pattern. RESEARCH QUESTION: What is the effect of wearing an ultrasound probe at the lower limb in adolescents with cerebral palsy and typically developing peers? METHODS: Eleven individuals with cerebral palsy and nine age-matched typically developing peers walking barefoot at their self-selected speed were analyzed. Data collection occurred under three conditions: the reference condition (GAIT), and two conditions involving placement of the ultrasound probe over the distal medial gastrocnemius-Achilles tendon junction (MTJ) and over the medial gastrocnemius mid-belly to capture fascicles (FAS). Data processing included calculating differences between conditions using root mean square error (RMSE) for joint kinematics and comparing them to the overall mean difference. Additionally, Spearman correlations were calculated to examine the relationship between kinematic RMSEs and walking speed. RESULTS: No significant differences in stance phase duration or walking speed were observed among the three conditions. Average RMSEs were below 5° for all parameters and condition comparisons in both groups. In both the TD and CP groups, RMSE values during the swing phase were higher than those during the stance phase for all joints. No significant correlations were found between height or body mass and swing phase RMSEs. In the CP group, there was a significant correlation between joint kinematics RMSEs and differences in walking speed at the hip, knee and ankle joints when comparing the MTJ condition with the GAIT condition. SIGNIFICANCE: This study confirms joint kinematics alterations are smaller than 5° due to wearing to the leg an ultrasound probe during walking.

The value of dynamic FDG PET/CT in the differential diagnosis of lung cancer and predicting EGFR mutations.

OBJECTIVES: 18F-fluorodeoxyglucose (FDG) PET/CT has been widely used for the differential diagnosis of cancer. Semi-quantitative standardized uptake value (SUV) is known to be affected by multiple factors and may make it difficult to differentiate between benign and malignant lesions. It is crucial to find reliable quantitative metabolic parameters to further support the diagnosis. This study aims to evaluate the value of the quantitative metabolic parameters derived from dynamic FDG PET/CT in the differential diagnosis of lung cancer and predicting epidermal growth factor receptor (EGFR) mutation status. METHODS: We included 147 patients with lung lesions to perform FDG PET/CT dynamic plus static imaging with informed consent. Based on the results of the postoperative pathology, the patients were divided into benign/malignant groups, adenocarcinoma (AC)/squamous carcinoma (SCC) groups, and EGFR-positive (EGFR+)/EGFR-negative (EGFR-) groups. Quantitative parameters including K1, k2, k3, and Ki of each lesion were obtained by applying the irreversible two-tissue compartmental modeling using an in-house Matlab software. The SUV analysis was performed based on conventional static scan data. Differences in each metabolic parameter among the group were analyzed. Wilcoxon rank-sum test, independent-samples T-test, and receiver-operating characteristic (ROC) analysis were performed to compare the diagnostic effects among the differentiated groups. P < 0.05 were considered statistically significant for all statistical tests. RESULTS: In the malignant group (N = 124), the SUVmax, k2, k3, and Ki were higher than the benign group (N = 23), and all had-better performance in the differential diagnosis (P < 0.05, respectively). In the AC group (N = 88), the SUVmax, k3, and Ki were lower than in the SCC group, and such differences were statistically significant (P < 0.05, respectively). For ROC analysis, Ki with cut-off value of 0.0250 ml/g/min has better diagnostic specificity than SUVmax (AUC = 0.999 vs. 0.70). In AC group, 48 patients further underwent EGFR testing. In the EGFR (+) group (N = 31), the average Ki (0.0279 ± 0.0153 ml/g/min) was lower than EGFR (-) group (N = 17, 0.0405 ± 0.0199 ml/g/min), and the difference was significant (P < 0.05). However, SUVmax and k3 did not show such a difference between EGFR (+) and EGFR (-) groups (P>0.05, respectively). For ROC analysis, the Ki had a cut-off value of 0.0350 ml/g/min when predicting EGFR status, with a sensitivity of 0.710, a specificity of 0.588, and an AUC of 0.674 [0.523-0.802]. CONCLUSION: Although both techniques were specific, Ki had a greater specificity than SUVmax when the cut-off value was set at 0.0250 ml/g/min for the differential diagnosis of lung cancer. At a cut-off value of 0.0350 ml/g/min, there was a 0.710 sensitivity for EGFR status prediction. If EGFR testing is not available for a patient, dynamic imaging could be a valuable non-invasive screening method.

Augmented Stress Weight-bearing CT for Evaluation of Subtle Lisfranc Injuries in the Elite Athlete.

BACKGROUND: Lisfranc injuries refer to a disruption or displacement of the tarsometatarsal joint of the foot. Subtle Lisfranc injuries can go undiagnosed on conventional imaging leading to devastating consequences and poor functional outcomes for elite athletes. Objective. The objective of this case study is to present a novel imaging technique using weight-bearing computed tomography (CT) with enhanced stress to identify subtle, dynamically unstable Lisfranc injuries. We illustrate this with a case presentation of an elite athlete who ultimately required surgical fixation for a subtle Lisfranc injury. MATERIALS AND METHODS: To perform an augmented stress weight-bearing CT, the patient was positioned standing, with their feet facing forward, and weight equally distributed. The patient was then coached to symmetrically raise both heels from the scanner platform. This plantarflexion provided augmented stress on the midfoot, allowing for more sensitive imaging of the Lisfranc injury. The weight-bearing CT and augmented stress images undergo 3D reconstruction and postprocessing to render coronal and sagittal images, allowing for comparison of the standard weight-bearing and augmented stress images. RESULTS: We present the case of a 22-year-old collegiate football lineman sustaining a Lisfranc injury. The injury diagnosis was made by magnetic resonance imaging (MRI) and clinical examination, without evidence of injury on weight-bearing XR or standard weight-bearing CT. With augmented stress CT imaging, the Lisfranc instability was noted, leading to surgical fixation, and return to sport the next season. CONCLUSION: We propose this technique for diagnosing subtle, unstable Lisfranc injuries where clinical suspicion persists despite inconclusive imaging, particularly in elite athletes. Further research is needed with larger sample sizes to investigate the sensitivity of this novel imaging technique for the detection of Lisfranc injury. LEVELS OF EVIDENCE: Level 4: Case Report.

Increased lesion detectability in patients with locally advanced breast cancer-A pilot study using dynamic whole-body [18F]FDG PET/CT.

BACKGROUND: Accurate diagnosis of axillary lymph node (ALN) metastases is essential for prognosis and treatment planning in breast cancer. Evaluation of ALN is done by ultrasound, which is limited by inter-operator variability, and by sentinel lymph node biopsy and/or ALN dissection, none of which are without risks and/or long-term complications. It is known that conventional 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has limited sensitivity for ALN metastases. However, a recently developed dynamic whole-body (D-WB) [18F]FDG PET/CT scanning protocol, allowing for imaging of tissue [18F]FDG metabolic rate (MRFDG), has been shown to have the potential to increase lesion detectability. The study purpose was to examine detectability of malignant lesions in D-WB [18F]FDG PET/CT compared to conventional [18F]FDG PET/CT. RESULTS: This study prospectively included ten women with locally advanced breast cancer who were referred for an [18F]FDG PET/CT as part of their diagnostic work-up. They all underwent D-WB [18F]FDG PET/CT, consisting of a 6 min single bed dynamic scan over the chest region started at the time of tracer injection, a 64 min dynamic WB PET scan consisting of 16 continuous bed motion passes, and finally a contrast-enhanced CT scan, with generation of MRFDG parametric images. Lesion visibility was assessed by tumor-to-background and contrast-to-noise ratios using volumes of interest isocontouring tumors with a set limit of 50% of SUVmax and background volumes placed in the vicinity of tumors. Lesion visibility was best in the MRFDG images, with target-to-background values 2.28 (95% CI: 2.04-2.54) times higher than target-to-background values in SUV images, and contrast-to-noise values 1.23 (95% CI: 1.12-1.35) times higher than contrast-to-noise values in SUV images. Furthermore, five imaging experts visually assessed the images and three additional suspicious lesions were found in the MRFDG images compared to SUV images; one suspicious ALN, one suspicious parasternal lymph node, and one suspicious lesion located in the pelvic bone. CONCLUSIONS: D-WB [18F]FDG PET/CT with MRFDG images show potential for improved lesion detectability compared to conventional SUV images in locally advanced breast cancer. Further validation in larger cohorts is needed. CLINICAL TRIAL REGISTRATION: The trial is registered in clinicaltrials.gov, NCT05110443, https://www. CLINICALTRIALS: gov/study/NCT05110443?term=NCT05110443&rank=1 .

Distribution of insulin in primate brain following nose-to-brain transport.

Introduction: Nose-to-brain (N2B) insulin delivery has potential for Alzheimer's disease (AD) therapy. However, clinical implementation has been challenging without methods to follow N2B delivery non-invasively. Positron emission tomography (PET) was applied to measure F-18-labeled insulin ([18F]FB-insulin) from intranasal dosing to brain uptake in non-human primates following N2B delivery. Methods: [18F]FB-insulin was prepared by reacting A1,B29-di(tert-butyloxycarbonyl)insulin with [18F]-N-succinimidyl-4-fluorobenzoate. Three methods of N2B delivery for [18F]FB-insulin were compared - delivery as aerosol via tubing (rhesus macaque, n = 2), as aerosol via preplaced catheter (rhesus macaque, n = 3), and as solution via preplaced catheter (cynomolgus macaque, n = 3). Following dosing, dynamic PET imaging (120 min) quantified delivery efficiency to the nasal cavity and whole brain. Area under the time-activity curve was calculated for 46 regions of the cynomolgus macaque brain to determine regional [18F]FB-insulin levels. Results: Liquid instillation of [18F]FB-insulin by catheter outperformed aerosol methods for delivery to the subject (39.89% injected dose vs 10.03% for aerosol via tubing, 0.17% for aerosol by catheter) and subsequently to brain (0.34% injected dose vs 0.00020% for aerosol via tubing, 0.05% for aerosol by catheter). [18F]FB-insulin was rapidly transferred across the cribriform plate to limbic and frontotemporal areas responsible for emotional and memory processing. [18F]FB-insulin half-life was longer in olfactory nerve projection sites with high insulin receptor density compared to the whole brain. Discussion: The catheter-based liquid delivery approach combined with PET imaging successfully tracked the fate of N2B [18F]FB-insulin and is thought to be broadly applicable for assessments of other therapeutic agents. This method can be rapidly applied in humans to advance clinical evaluation of N2B insulin as an AD therapeutic. Highlights for: [18F]FB-insulin passage across the cribriform plate was detected by PET.Intranasal [18F]FB-insulin reached the brain within 13 min.[18F]FB-insulin activity was highest in emotional and memory processing regions.Aerosol delivery was less efficient than liquid instillation by preplaced catheter.Insulin delivery to the cribriform plate was critical for arrival in the brain.

CT respiratory motion synthesis using joint supervised and adversarial learning.

Objective.Four-dimensional computed tomography (4DCT) imaging consists in reconstructing a CT acquisition into multiple phases to track internal organ and tumor motion. It is commonly used in radiotherapy treatment planning to establish planning target volumes. However, 4DCT increases protocol complexity, may not align with patient breathing during treatment, and lead to higher radiation delivery.Approach.In this study, we propose a deep synthesis method to generate pseudo respiratory CT phases from static images for motion-aware treatment planning. The model produces patient-specific deformation vector fields (DVFs) by conditioning synthesis on external patient surface-based estimation, mimicking respiratory monitoring devices. A key methodological contribution is to encourage DVF realism through supervised DVF training while using an adversarial term jointly not only on the warped image but also on the magnitude of the DVF itself. This way, we avoid excessive smoothness typically obtained through deep unsupervised learning, and encourage correlations with the respiratory amplitude.Main results.Performance is evaluated using real 4DCT acquisitions with smaller tumor volumes than previously reported. Results demonstrate for the first time that the generated pseudo-respiratory CT phases can capture organ and tumor motion with similar accuracy to repeated 4DCT scans of the same patient. Mean inter-scans tumor center-of-mass distances and Dice similarity coefficients were 1.97 mm and 0.63, respectively, for real 4DCT phases and 2.35 mm and 0.71 for synthetic phases, and compares favorably to a state-of-the-art technique (RMSim).Significance.This study presents a deep image synthesis method that addresses the limitations of conventional 4DCT by generating pseudo-respiratory CT phases from static images. Although further studies are needed to assess the dosimetric impact of the proposed method, this approach has the potential to reduce radiation exposure in radiotherapy treatment planning while maintaining accurate motion representation. Our training and testing code can be found athttps://github.com/cyiheng/Dynagan.

Confounding factors in peripheral thermal recovery time after active cooling.

OBJECTIVES: The effectiveness of normal physiological thermoregulation complicates differentiation between pathologic changes in medical thermography associated with peripheral artery disease and a number of other clinical conditions. In this study we investigate a number of potential confounding factors to the thermal recovery rate after active limb cooling, with the main focus on age and sex. APPROACH: The source data consists of 53 healthy individuals with no diagnosed cardiovascular disease or reported symptoms and with a mean age of 38.4 (± 12.1) years. The sample population was further divided into male (N = 14) and female groups (N = 39). The thermal recovery time was measured using two thermal cameras from both lower limbs on plantar and dorsal sides. The active cooling was achieved using moldable cold pads placed on the plantar and dorsal side of the lower limb. The recovery was measured until the temperature had reached a stable level. The recovery time was determined from an exponential fit to the measured data. RESULTS: The correlation between the thermal recovery time constant and age varied from low to moderate linear correlation (0.31 ≤ ⍴ ≤ 70), depending on the inspected region of interest, with a higher statistically significant correlation in the medial regions. The contralateral limb temperature differences or the thermal time constants did not have statistically significant differences between the male and female sexes. Further, the secondary metrics such as participant's body mass, body-mass index, or systolic blood pressure had low or no correlation with the thermal recovery time in the study group. CONCLUSION: The thermal recovery time constant after active cooling appears as a relatively independent metric from the majority of the measured potential confounding factors. Age should be accounted for when performing thermal recovery measurements. However, dynamic thermal imaging and its methodologies require further research and exploration.

Hybrid dynamic bright and black blood angiography by non-contrast-enhanced vessel selective saturation angiography.

The integrity of vessel walls and changes in blood flow are involved in many diseases, and information about these anatomical and physiological conditions is important for a diagnosis. There are several different angiography methods that can be used to generate images for diagnostic purposes, but often using different imaging techniques and MR sequences. The purpose of this study was to develop a method that allows time-resolved, vessel-selective simultaneous bright and black blood imaging by vesselselective blood saturation. Measurements in six volunteers were performed to evaluate the time-resolved bright blood angiography and the significance of the generated black blood contrast. It was shown that this method can be used to generate a black blood contrast with a sufficient signal difference to the surrounding gray matter in addition to the time-resolved and vessel-selective bright blood contrast. Using post-processing methods, whole brain angiograms can be calculated from the acquired data.

Single-shot Echo Planar Time-resolved Imaging for multi-echo functional MRI and distortion-free diffusion imaging.

Purpose: To develop EPTI, a multi-shot distortion-free multi-echo imaging technique, into a single-shot acquisition to achieve improved robustness to motion and physiological noise, increased temporal resolution, and high SNR efficiency for dynamic imaging applications. Methods: A new spatiotemporal encoding was developed to achieve single-shot EPTI by enhancing spatiotemporal correlation in k-t space. The proposed single-shot encoding improves reconstruction conditioning and sampling efficiency, with additional optimization under various accelerations to achieve optimized performance. To achieve high SNR efficiency, continuous readout with minimized deadtime was employed that begins immediately after excitation and extends for an SNR-optimized length. Moreover, k-t partial Fourier and simultaneous multi-slice acquisition were integrated to further accelerate the acquisition and achieve high spatial and temporal resolution. Results: We demonstrated that ss-EPTI achieves higher tSNR efficiency than multi-shot EPTI, and provides distortion-free imaging with densely-sampled multi-echo images at resolutions ~1.25-3 mm at 3T and 7T-with high SNR efficiency and with comparable temporal resolutions to ss-EPI. The ability of ss-EPTI to eliminate dynamic distortions common in EPI also further improves temporal stability. For fMRI, ss-EPTI also provides early-TE images (e.g., 2.9ms) to recover signal-intensity and functional-sensitivity dropout in challenging regions. The multi-echo images provide TE-dependent information about functional fluctuations, successfully distinguishing noise-components from BOLD signals and further improving tSNR. For diffusion MRI, ss-EPTI provides high-quality distortion-free diffusion images and multi-echo diffusion metrics. Conclusion: ss-EPTI provides distortion-free imaging with high image quality, rich multi-echo information, and enhanced efficiency within comparable temporal resolution to ss-EPI, offering a robust and efficient acquisition for dynamic imaging.

Portable Dynamic Chest Radiography: Literature Review and Potential Bedside Applications.

Dynamic digital radiography (DDR) is a high-resolution radiographic imaging technique using pulsed X-ray emission to acquire a multiframe cine-loop of the target anatomical area. The first DDR technology was orthostatic chest acquisitions, but new portable equipment that can be positioned at the patient's bedside was recently released, significantly expanding its potential applications, particularly in chest examination. It provides anatomical and functional information on the motion of different anatomical structures, such as the lungs, pleura, rib cage, and trachea. Native images can be further analyzed with dedicated post-processing software to extract quantitative parameters, including diaphragm motility, automatically projected lung area and area changing rate, a colorimetric map of the signal value change related to respiration and motility, and lung perfusion. The dynamic diagnostic information along with the significant advantages of this technique in terms of portability, versatility, and cost-effectiveness represents a potential game changer for radiological diagnosis and monitoring at the patient's bedside. DDR has several applications in daily clinical practice, and in this narrative review, we will focus on chest imaging, which is the main application explored to date in the literature. However, studies are still needed to understand deeply the clinical impact of this method.

Mantis: high-throughput 4D imaging and analysis of the molecular and physical architecture of cells.

High-throughput dynamic imaging of cells and organelles is essential for understanding complex cellular responses. We report Mantis, a high-throughput 4D microscope that integrates two complementary, gentle, live-cell imaging technologies: remote-refocus label-free microscopy and oblique light-sheet fluorescence microscopy. Additionally, we report shrimPy, an open-source software for high-throughput imaging, deconvolution, and single-cell phenotyping of 4D data. Using Mantis and shrimPy, we achieved high-content correlative imaging of molecular dynamics and the physical architecture of 20 cell lines every 15 minutes over 7.5 hours. This platform also facilitated detailed measurements of the impacts of viral infection on the architecture of host cells and host proteins. The Mantis platform can enable high-throughput profiling of intracellular dynamics, long-term imaging and analysis of cellular responses to perturbations, and live-cell optical screens to dissect gene regulatory networks.

Spatiotemporal image reconstruction to enable high-frame-rate dynamic photoacoustic tomography with rotating-gantry volumetric imagers.

Significance: Dynamic photoacoustic computed tomography (PACT) is a valuable imaging technique for monitoring physiological processes. However, current dynamic PACT imaging techniques are often limited to two-dimensional spatial imaging. Although volumetric PACT imagers are commercially available, these systems typically employ a rotating measurement gantry in which the tomographic data are sequentially acquired as opposed to being acquired simultaneously at all views. Because the dynamic object varies during the data-acquisition process, the sequential data-acquisition process poses substantial challenges to image reconstruction associated with data incompleteness. The proposed image reconstruction method is highly significant in that it will address these challenges and enable volumetric dynamic PACT imaging with existing preclinical imagers. Aim: The aim of this study is to develop a spatiotemporal image reconstruction (STIR) method for dynamic PACT that can be applied to commercially available volumetric PACT imagers that employ a sequential scanning strategy. The proposed reconstruction method aims to overcome the challenges caused by the limited number of tomographic measurements acquired per frame. Approach: A low-rank matrix estimation-based STIR (LRME-STIR) method is proposed to enable dynamic volumetric PACT. The LRME-STIR method leverages the spatiotemporal redundancies in the dynamic object to accurately reconstruct a four-dimensional (4D) spatiotemporal image. Results: The conducted numerical studies substantiate the LRME-STIR method's efficacy in reconstructing 4D dynamic images from tomographic measurements acquired with a rotating measurement gantry. The experimental study demonstrates the method's ability to faithfully recover the flow of a contrast agent with a frame rate of 10 frames per second, even when only a single tomographic measurement per frame is available. Conclusions: The proposed LRME-STIR method offers a promising solution to the challenges faced by enabling 4D dynamic imaging using commercially available volumetric PACT imagers. By enabling accurate STIRs, this method has the potential to significantly advance preclinical research and facilitate the monitoring of critical physiological biomarkers.